Targeting CD300ld to normalize the tumor microenvironment: an emerging insight in cancer immunotherapy.

In a recent Nature elegant study, Wang et al. identified CD300ld, a novel functionally highly conserved tumor immunosuppressive receptor, highly expressed specifically on polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), as well as a key receptor in the regulation of recruitment and immunosuppressive function of PMN-MDSCs. Targeting CD300ld could remodel the tumor immune microenvironment, resulting in a broad-spectrum anti-tumor effect.

Happy people are always similar: The evidence from brain morphological and functional inter-subject correlations.

A fundamental question in the study of happiness is whether there is neural evidence to support a well-known hypothesis that happy people are always similar while unfortunate people have their own misfortunes. To investigate this, we employed several happiness-related questionnaires to identify potential components of happiness, and further investigated and confirmed their associations with personality, mood, aggressive behaviors, and amygdala reactivity to fearful faces within a substantial sample size of college students (n = 570). Additionally, we examined the functional and morphological similarities and differences among happy individuals using the inter-subject representational similarity analysis (IS-RSA). IS-RSA emphasizes the geometric properties in a high-dimensional space constructed by brain or behavioral patterns and focuses on individual subjects. Our behavioral findings unveiled two factors of happiness: individual and social, both of which mediated the effect of personality traits on individual aggression. Subsequently, mood mediated the impact of happiness on aggressive behaviors across two subgroup splits. Functional imaging data revealed that individuals with higher levels of happiness exhibited reduced amygdala reactivity to fearful faces, as evidenced by a conventional face-matching task (n = 104). Moreover, IS-RSA demonstrated that these participants manifested similar neural activation patterns when processing fearful faces within the visual pathway, but not within the emotional network (e.g., amygdala). Morphological observations (n = 425) indicated that individuals with similar high happiness levels exhibited comparable gray matter volume patterns within several networks, including the default mode network, fronto-parietal network, visual network, and attention network. Collectively, these findings offer early neural evidence supporting the proposition that happy individuals may share common neural characteristics.

Long-Term Visit-to-Visit Blood Pressure Variability and Cognitive Decline Among Patients With Hypertension: A Pooled Analysis of 3 National Prospective Cohorts.

BACKGROUND: A limited number of studies investigated the association between blood pressure variability (BPV) and cognitive impairment in patients with hypertension. This study aimed to identify the longitudinal association between BPV and cognitive decline and the role of blood pressure (BP) control in this association. METHODS AND RESULTS: Participants with hypertension from the HRS (Health and Retirement Study), the ELSA (English Longitudinal Study of Ageing), and the CHARLS (China Health and Retirement Longitudinal Study) were included. Variation independent of the mean (VIM) was adopted to measure BPV. Cognitive function was measured by standard questionnaires, and a standardized Z score was calculated. Linear mixed-model and restricted cubic splines were adopted to explore the association between BPV and cognitive decline. The study included 4853, 1616, and 1432 eligible patients with hypertension from the HRS, ELSA, and CHARLS, respectively. After adjusting for covariates, per-SD increment of VIM of BP was significantly associated with global cognitive function decline in Z scores in both systolic BP (pooled ß, -0.045 [95% CI, -0.065 to -0.029]) and diastolic BP (pooled ß, -0.022 [95% CI, -0.040 to -0.004]) among hypertensive patients. Similar inverse associations were observed in patients with hypertension taking antihypertensive drugs and in patients with hypertension with well-controlled BP. CONCLUSIONS: High BPV was independently associated with a faster cognitive decline among patients with hypertension, even those with antihypertensive medications or well-controlled BP. Further studies are needed to confirm our results and determine whether reducing BPV can prevent or delay cognitive decline.

The Impact of Dual-Tasks and Disease Severity on Posture, Gait, and Functional Mobility among People Living with Dementia in Residential Care Facilities: A Pilot Study.

Gait speed and timed-up-and-go (TUG) predict cognitive decline, falls, and mortality. Dual-tasks may be useful in cognitive screening among people living with dementia (PWD), but more evidence is needed. This cross-sectional study aimed to compare single- and dual-task performance and determine the influence of dementia severity on dual-task performance and interference. Thirty PWD in two residential care facilities (Age: 81.3 ± 7.1 years; Montreal Cognitive Assessment: 10.4 ± 6.0 points) completed two trials of single- (feet apart) and dual-task posture (feet apart while counting backward), single- (walk 4 m) and dual-task gait (walk 4m while naming words), and single- (timed-up-and-go (TUG)), and dual-task functional mobility (TUG while completing a category task) with APDM inertial sensors. Dual-tasks resulted in greater sway frequency, jerk, and sway area; slower gait speed; greater double limb support; shorter stride length; reduced mid-swing elevation; longer TUG duration; reduced turn angle; and slower turn velocity than single-tasks (ps < 0.05). Dual-task performance was impacted (reduced double limb support, greater mid-swing elevation), and dual-task interference (greater jerk, faster gait speed) was related to moderate-to-severe compared to mild PWD. Moderate-to-severe PWD had poorer dynamic stability and a reduced ability to appropriately select a cautious gait during dual-tasks than those with mild PWD, indicating the usefulness of dual-tasks for cognitive screening.

Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Review of robotic systems for thoracoabdominal puncture interventional surgery.

Cancer, with high morbidity and high mortality, is one of the major burdens threatening human health globally. Intervention procedures via percutaneous puncture have been widely used by physicians due to its minimally invasive surgical approach. However, traditional manual puncture intervention depends on personal experience and faces challenges in terms of precisely puncture, learning-curve, safety and efficacy. The development of puncture interventional surgery robotic (PISR) systems could alleviate the aforementioned problems to a certain extent. This paper attempts to review the current status and prospective of PISR systems for thoracic and abdominal application. In this review, the key technologies related to the robotics, including spatial registration, positioning navigation, puncture guidance feedback, respiratory motion compensation, and motion control, are discussed in detail.

Experimental demonstration on 400†nm-scale bandwidth optical parametric chirped-pulse amplification based on mixed cascaded crystals.

We present an optical parametric chirped-pulse amplification (OPCPA) based on mixed cascaded crystals, taking advantage of the unique parametric phase-matching of lithium triborate (LiB3O5, LBO) and yttrium calcium oxyborate ((YCa4O(BO3)3, YCOB) crystals. The OPCPA properties of LBO at 880 nm and YCOB at 750 nm are studied respectively. After amplification by two LBO and two YCOB crystals, a total signal gain of 108 and spectral bandwidth close to 400 nm is obtained. After accurate dispersion compensation with a grating-pair compressor and chirped mirror compensator, a pulse duration of 9.4 fs is obtained by a SHG-frequency-resolved optical grating (FROG). This approach will be of great significance in high energy amplifier for high peak power few-cycle laser sources.

Locoregional therapies for hepatocellular carcinoma: The current status and future perspectives.

Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer-related mortality. Locoregional therapies (LRTs) play a crucial role in HCC management and are selectively adopted in real-world practice across various stages. Choosing the best form of LRTs depends on technical aspects, patient clinical status and tumour characteristics. Previous studies have consistently highlighted the efficacy of combining LRTs with molecular targeted agents in HCC treatment. Recent studies propose that integrating LRTs with immune checkpoint inhibitors and molecular targeted agents could provide substantial therapeutic benefits, a notion underpinned by both basic and clinical evidence. This review summarised the current landscape of LRTs in HCC and discussed the anticipated outcomes of combinations with immunotherapy regimens.

Transarterial Chemoembolization with Epirubicin-Loaded Microspheres for Hepatocellular Carcinoma: A Prospective, Single-Arm, Multicenter, Phase 2 Study (STOPPER Trial).

PURPOSE: While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 µm) microspheres loaded with epirubicin. MATERIALS AND METHODS: This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30-50), 75 (range, 60-90), or 100 (range, 75-125) µm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events. RESULTS: Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death. CONCLUSION: DEB-TACE using epirubicin-loaded small-sized (≤ 100 µm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC. TRIAL REGISTRATION: Clinicaltrials.gov NCT03113955; registered April 14, 2017. Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017. LEVEL OF EVIDENCE: 2, Prospective, Non-randomized, Single-arm, study.

Exploring the Association Between Physical Activity and Cognitive Function Among People Living with Dementia.

Background: Physical activity preserves cognitive function in people without dementia, but the relationship between physical activity and cognitive domains among people living with dementia is unclear. Objective: The objective of this study was to explore the association between physical activity and cognition domains among people living with dementia. Methods: Participants living with dementia in residential care facilities (complete case analysis: n = 24/42) completed a battery of cognitive tests (global cognition: Montreal Cognitive Assessment; executive function: Trail-Making Test, Digit Span Forward Test; perception and orientation: Benton Judgement of Line Orientation Test; language: Boston Naming Test; learning and memory: Rey Auditory Verbal Learning Test; complex attention: Digit Symbol Substitution Test). Participants wore an actigraphy monitor on their non-dominant wrist over seven days. We conducted a linear regression for total physical activity (independent variable) with race (white/black), fall risk (Morse Fall Scale), and the number of comorbidities (Functional Comorbidities Index) as covariates, and cognitive tests as variables of interest. Results: Participants were primarily male (75%), white (87.5%), and 50%had unspecified dementia (Alzheimer's disease: 33%). Greater physical activity was associated with poorer global cognition, better executive function, and better learning and memory (ps <  0.05). Physical activity was not related to visuospatial perception, language, or complex attention. Conclusions: Physical activity may preserve executive function and learning and memory among people living with dementia. Wandering is more common in later stages of dementia, which may explain greater physical activity observed with lower global cognition. Regularly assessing physical activity may be useful in screening and monitoring cognitive changes.

New First-line Immunotherapy-based Therapies for Unresectable Hepatocellular Carcinoma: A Living Network Meta-analysis.

Background and Aims: Several first-line immune checkpoint inhibitor (ICI)-based combination therapies have been identified for unresectable hepatocellular carcinoma (uHCC). This network meta-analysis (NMA) aimed to provide the most updated evidence about the preferred first-line ICI-based regimens for uHCC. Methods: A comprehensive literature search was performed in various databases from database inception to May 2022. The phase 3 trials evaluating first-line single-agent ICIs, molecular-target agents (MTAs), or their combinations in uHCC were included. The main endpoints were overall survival (OS) and progression-free survival (PFS). Pooled effect estimates were calculated using a random effects model within the frequentist framework. Subgroup analyses based on etiology were also conducted. Results: Twelve trials at low risk of bias with 8,275 patients comparing 13 treatments were included. OS with atezolizumab plus bevacizumab was comparable to sintilimab plus IBI305 [hazard ratio (HR): 1.16; 95% confidence interval (CI): 0.80-1.68] and camrelizumab plus apatinib (HR: 1.06; 95% CI: 0.75-1.51). The combination therapies, apart from atezolizumab plus cabozantinib in OS and durvalumab plus tremelimumab in PFS, had higher P-score than single-agent MTAs or ICIs. The survival benefits were associated with a high risk of adverse events leading to treatment discontinuation. The proportion of patients with hepatitis B virus-related HCC receiving ICIs combinations might positively correlate with survival advantages (R2=0.8039, p=0.0155). Conclusion: This NMA demonstrated that atezolizumab plus bevacizumab remains the stand of care and confers comparable survival benefits to sintilimab plus IBI305 and camrelizumab plus apatinib in first-line therapy for uHCC. The optimal treatment algorithms should consider efficacy, safety, and etiology.

Baseline characteristics and the factors influencing successful smoking cessation: A comparison between a WeChat smoking cessation mini-program and an offline smoking cessation clinic.

INTRODUCTION: Smoking cessation (SC) clinics are a professional SC services in China. However, studies comparing the characteristics and SC rates of smoking populations in SC clinics with those using mobile SC programs are limited. We compared smokers' characteristics, 3-month SC rates, and the factors influencing 3-month SC success, between a large hospital SC clinic and a WeChat SC mini-program. METHODS: Between January and November 2021, 384 participants voluntarily enrolled in either the hospital SC clinic (Group A: n=243) or the WeChat SC mini-program (Group B: n=141). Both groups underwent a 3-month SC intervention, and their SC status was monitored at 24 hours, 1 week, 1 month, and 3 months after quitting. SC rate was defined as the self-reported rate of continuous SC. RESULTS: The 3-month SC rate was higher in Group A (42.4%) than in Group B (24.8%). Participants with middle school education had a lower likelihood of SC success than those with primary school or lower (p=0.014). Employees in the enterprise/business/services industries were more likely to have SC success than farmers (p=0.013). Participants with SC difficulty scores of 0-60 were more successful than those with scores >60 (p=0.001, p=0.000, respectively). Participants who quit smoking due to their illness, or other reasons, had a higher likelihood of SC success than those who quit due to concerns about their own and their family's health (p=0.006, p=0.098, respectively). While the likelihood of SC success was lower in those who quit because of the influence of their environment than in those who quit due to concerns about their own and their family's health (p=0.057). CONCLUSIONS: Both SC clinics and WeChat SC mini-programs achieved satisfactory SC rates. The high accessibility of mobile SC platforms, which save time spent on transportation and medical visits, renders them worth promoting and publicizing as additional SC options for smokers, particularly young smokers.

All-in-one properties of an anticancer-covered airway stent for the prevention of malignant central airway obstruction.

Malignant central airway obstruction (MCAO) resulting from tumor metastasis and compression severely impairs respiration, posing life-threatening risks. To address this, we employed a synergistic modification strategy, combining cisplatin (CIS) and silver nanoparticles (AgNPs). Polycaprolactone (PCL) served as a drug carrier, enabling the preparation of a functional CIS@AgNPs@PCL fiber membrane-covered airway stent via electrospinning. This approach aimed to enhance the patency rate of MCAO. Characterization via ATR-FTIR, scanning electron microscope-energy-dispersive spectroscopy, and transmission electron microscope confirmed successful immobilization of CIS and AgNPs onto the stent surface. CIS@AgNPs@PCL substantially suppressed non-small cell lung cancer cells (A549), causing DNA damage, ultrastructural disruption, and over 50% apoptosis in 48 h. It also displayed potent antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans biofilms. A mouse subcutaneous tumor recurrence model assessed anti-cancer efficacy. CIS@AgNPs@PCL fiber-covered stents significantly inhibited lung cancer tissue and enhanced anti-cancer effects by up-regulating caspase-3 and Bax, while down-regulating Bcl-2. This study's functional airway stent provides a proof-of-concept for an integrated anti-cancer and antibacterial strategy. It promptly restores the lumen, inhibits biofilm formation, prevents tumor progression, and improves postoperative MCAO patency.

Real-world efficacy and safety of TACE plus camrelizumab and apatinib in patients with HCC (CHANCE2211): a propensity score matching study.

OBJECTIVES: This study aimed to investigate the efficacy and safety of transarterial chemoembolization (TACE) plus camrelizumab, a monoclonal antibody targeting programmed death-1, and apatinib for patients with intermediate and advanced hepatocellular carcinoma (HCC) in a real-world setting. METHODS: A total of 586 HCC patients treated with either TACE plus camrelizumab and apatinib (combination group, n = 107) or TACE monotherapy (monotherapy group, n = 479) were included retrospectively. Propensity score matching analysis was used to match patients. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety in the combination group were described in comparison to monotherapy. RESULTS: After propensity score matching (1:2), 84 patients in the combination group were matched to 147 patients in the monotherapy group. The median age was 57 years and 71/84 (84.5%) patients were male in the combination group, while the median age was 57 years with 127/147 (86.4%) male in the monotherapy group. The median OS, PFS, and ORR in the combination group were significantly higher than those in the monotherapy group (median OS, 24.1 vs. 15.7 months, p = 0.008; median PFS, 13.5 vs. 7.7 months, p = 0.003; ORR, 59.5% [50/84] vs. 37.4% [55/147], p = 0.002). On multivariable Cox regression, combination therapy was associated with significantly better OS (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.26-0.64; p < 0.001) and PFS (adjusted HR, 0.52; 95% CI, 0.37-0.74; p < 0.001). Grade 3 or 4 adverse events occurred in 14/84 (16.7%) and 12/147 (8.2%) in the combination and monotherapy groups, respectively. CONCLUSIONS: TACE plus camrelizumab and apatinib showed significantly better OS, PFS, and ORR versus TACE monotherapy for predominantly advanced HCC. CLINICAL RELEVANCE STATEMENT: Compared with TACE monotherapy, TACE plus immunotherapy and molecular targeted therapy showed better clinical efficacy for predominantly advanced HCC patients, with a higher incidence of adverse events. KEY POINTS: • This propensity score-matched study demonstrates that TACE plus immunotherapy and molecular targeted therapy have a longer OS, PFS, and ORR compared with TACE monotherapy in HCC. • Grade 3 or 4 adverse events occurred in 14/84 (16.7%) patients treated with TACE plus immunotherapy and molecular targeted therapy compared with 12/147 (8.2%) patients in the monotherapy group, while no grade 5 adverse events were observed in all cohorts.

The Health and Economic Impact of Expanding Home Blood Pressure Monitoring.

INTRODUCTION: Home blood pressure monitoring is more convenient and effective than clinic-based monitoring in diagnosing and managing hypertension. Despite its effectiveness, there is limited evidence of the economic impact of home blood pressure monitoring. This study aims to fill this research gap by assessing the health and economic impact of adopting home blood pressure monitoring among adults with hypertension in the U.S. METHODS: A previously developed microsimulation model of cardiovascular disease was used to estimate the long-term impact of adopting home blood pressure monitoring versus usual care on myocardial infarction, stroke, and healthcare costs. Data from the 2019 Behavioral Risk Factor Surveillance System and the published literature were used to estimate model parameters. The averted cases of myocardial infarction and stroke and healthcare cost savings were estimated among the U.S. adult population with hypertension and in subpopulations defined by sex, race, ethnicity, and rural/urban area. The simulation analyses were conducted between February and August 2022. RESULTS: Compared with usual care, adopting home blood pressure monitoring was estimated to reduce myocardial infarction cases by 4.9% and stroke cases by 3.8% as well as saving an average of $7,794 in healthcare costs per person over 20 years. Non-Hispanic Blacks, women, and rural residents had more averted cardiovascular events and greater cost savings related to adopting home blood pressure monitoring compared with non-Hispanic Whites, men, and urban residents. CONCLUSIONS: Home blood pressure monitoring could substantially reduce the burden of cardiovascular disease and save healthcare costs in the long term, and the benefits could be more pronounced in racial and ethnic minority groups and those living in rural areas. These findings have important implications in expanding home blood pressure monitoring for improving population health and reducing health disparities.

The effects of strEngth aNd BaLance exercise on Executive function in people living with Dementia (ENABLED): Study protocol for a pilot randomized controlled trial.

BACKGROUND: Exercise may improve executive function among people living with all-cause dementia (PWD), but more evidence is needed. The aim of this pilot randomized controlled trial (RCT) is to examine whether exercise plus usual care improves the primary outcome of executive function, and secondary physiological (inflammation, metabolic aging, epigenetics) and behavioral (cognition, psychological health, physical function, and falls) outcomes compared to usual care alone among PWD. METHODS AND STUDY DESIGN: The strEngth aNd BaLance exercise on Executive function in people living with Dementia (ENABLED) protocol is a pilot parallel, 6-month assessor-blinded RCT (1:1) in residential care facilities, including n = 21 receiving exercise plus usual care and n = 21 usual care alone [NCT05488951]. We will collect primary (Color-Word Stroop Test) and secondary physiological (inflammation, metabolic aging, epigenetics) and behavioral (cognition, psychological health, physical function, and falls) outcomes at baseline and 6 months. We will obtain falls monthly from medical charts. We will collect physical activity, sedentary behavior, and sleep via wrist-worn accelerometers over 7 days at baseline and 6 months. The physical therapist-led adapted Otago Exercise Program will involve 1-h of strength, balance and walking 3×/week for 6 months in groups of 5-7. We will use generalized linear mixed models to examine differences over time in primary and secondary outcomes between groups and examine potential interactions with sex and race. DISCUSSION: This pilot RCT will examine the direct effects and potential underlying physiological mechanisms of exercise on executive function and other behavioral outcomes in PWD, which may have implications for clinical care management.

Irradiation stent with 125 I plus TACE versus sorafenib plus TACE for hepatocellular carcinoma with major portal vein tumor thrombosis: a multicenter randomized trial.

BACKGROUND AND AIM: Treatment strategy for hepatocellular carcinoma (HCC) and Vp4 [main trunk] portal vein tumor thrombosis (PVTT) remains limited due to posttreatment liver failure. We aimed to assess the efficacy of irradiation stent placement with 125 I plus transcatheter arterial chemoembolization (TACE) (ISP-TACE) compared to sorafenib plus TACE (Sora-TACE) in these patients. METHODS: In this multicenter randomized controlled trial, participants with HCC and Vp4 PVTT without extrahepatic metastases were enrolled from November 2018 to July 2021 at 16 medical centers. The primary endpoint was overall survival (OS). The secondary endpoints were hepatic function, time to symptomatic progression, patency of portal vein, disease control rate, and treatment safety. RESULTS: Of 105 randomized participants, 51 were assigned to the ISP-TACE group, and 54 were assigned to the Sora-TACE group. The median OS was 9.9 months versus 6.3 months (95% CI: 0.27-0.82; P =0.01). Incidence of acute hepatic decompensation was 16% (8 of 51) versus 33% (18 of 54) ( P =0.036). The time to symptomatic progression was 6.6 months versus 4.2 months (95% CI: 0.38-0.93; P =0.037). The median stent patency was 7.2 months (interquartile range, 4.7-9.3) in the ISP-TACE group. The disease control rate was 86% (44 of 51) versus 67% (36 of 54) ( P =0.018). Incidences of adverse events at least grade 3 were comparable between the safety populations of the two groups: 16 of 49 (33%) versus 18 of 50 (36%) ( P =0.73). CONCLUSION: Irradiation stent placement plus TACE showed superior results compared with sorafenib plus TACE in prolonging OS in patients with HCC and Vp4 PVTT.

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001).

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

Role of Transarterial Chemoembolization in the Treatment of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. According to the Barcelona Clinic Liver Cancer (BCLC) staging system, transarterial chemoembolization (TACE) is the first-line recommendation for intermediate-stage HCC. In real-world clinical practice, TACE also plays an important role in early- and advanced-stage HCC. This review article by the experts from Chinese Liver Cancer Clinical Study Alliance (CHANCE) summarizes the available clinical evidence pertaining to the current application of TACE in patients with early-, intermediate-, and advanced-stage HCC. In addition, combination of TACE with other treatment modalities, especially immunotherapy, is reviewed.

Effects of Vitamin D3 and Marine Omega-3 Fatty Acids Supplementation on Biomarkers of Systemic Inflammation: 4-Year Findings from the VITAL Randomized Trial.

Background: The VITAL study was a nationwide, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial of vitamin D3 (2000 IU/day) and marine n-3 FAs (1 g/day) supplements. We recently reported that vitamin D supplementation with or without omega 3 fatty acids reduced autoimmune disease by 22% in the VITAL study. Objective: To investigate the effects of vitamin D3 and/or n-3 FAs on changes in systemic inflammatory biomarkers including pro- and anti-inflammatory cytokines over a 4-year period in the VITAL sub-cohort with in-person evaluations at the Center for Clinical Investigations (CCI) in Boston. Design: Serum levels of four inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6, interleukin-10, and tumor necrosis factor-α) were measured in a total of 2713 samples from those 1054 VITAL/CCI participants (aged 64.9 ± 6.5 years, 49% female, 84% white, and 9% black) at baseline, year 2, and year 4 follow-up visits. Results: In multiple-adjusted models, vitamin D3 supplementation decreased serum hs-CRP levels by 19% at 2-year follow-up (nominal p = 0.007; p-value after multiple comparison adjustment = 0.028), but not at 4-year follow-up (nominal and adjusted p-values > 0.05). The effects of vitamin D3 on other inflammatory markers were not statistically significant either at year 2 or year 4 (all adjusted p-values > 0.05). Marine n-3 FAs were not significantly associated with changes of all the above inflammatory markers either at years 2 and 4, after multiple comparison adjustment (all p-values > 0.05). Conclusions: Vitamin D3 supplementation with or without n-3 FAs decreased hs-CRP by 19% at year 2, but not other inflammatory biomarkers at year 2 or year 4, while n-3 FAs with or without vitamin D3 did not significantly affect these biomarkers at either time point. Our findings support a potential role of vitamin D supplementation in modulating the chronic inflammatory process, systemic inflammation, and possibly autoimmune disease progression.